Emerging role of GIP and related gut hormones in fertility and PCOS

Moffett, R. Charlotte; Naughton, Violetta

doi:10.1016/j.peptides.2019.170233

Cited by 32 publications

(29 citation statements)

References 79 publications

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“…While innovation has witnessed the production of increasingly long-acting agents, multi-action unimolecular agonists and novel delivery methods (67,68,70,(73)(74)(75)(195)(196)(197), there is still a growing need for ever more effective agents to counter obesity, diabetes and a host of other degenerative diseases. Better understanding of the physiology of PGDPs and their various roles in the likes of cognition, bone turnover, cardiovascular function, fertility and liver function (157,174,185,334,368,369), may herald important future uses for proglucagon-derived therapeutics.…”

Section: Discussionmentioning

confidence: 99%

“…There is increasing evidence in support of incretin-analogue use in polycystic ovary syndrome (PCOS) ( 185 ), an endocrine disorder which greatly impacts fertility in women, with over 10% of women of reproductive age affected by the condition ( 186 ). PCOS is a metabolic disorder that has overlap with T2DM, with patients often being overweight, and presenting with symptoms such as severe insulin resistance, hyperinsulinaemia and dyslipidaemia ( 187 ).…”

Section: Glucagon-like Peptide-1mentioning

confidence: 99%

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Proglucagon-Derived Peptides as Therapeutics

et al. 2021

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Initially discovered as an impurity in insulin preparations, our understanding of the hyperglycaemic hormone glucagon has evolved markedly over subsequent decades. With description of the precursor proglucagon, we now appreciate that glucagon was just the first proglucagon-derived peptide (PGDP) to be characterised. Other bioactive members of the PGDP family include glucagon-like peptides -1 and -2 (GLP-1 and GLP-2), oxyntomodulin (OXM), glicentin and glicentin-related pancreatic peptide (GRPP), with these being produced via tissue-specific processing of proglucagon by the prohormone convertase (PC) enzymes, PC1/3 and PC2. PGDP peptides exert unique physiological effects that influence metabolism and energy regulation, which has witnessed several of them exploited in the form of long-acting, enzymatically resistant analogues for treatment of various pathologies. As such, intramuscular glucagon is well established in rescue of hypoglycaemia, while GLP-2 analogues are indicated in the management of short bowel syndrome. Furthermore, since approval of the first GLP-1 mimetic for the management of Type 2 diabetes mellitus (T2DM) in 2005, GLP-1 therapeutics have become a mainstay of T2DM management due to multifaceted and sustainable improvements in glycaemia, appetite control and weight loss. More recently, longer-acting PGDP therapeutics have been developed, while newfound benefits on cardioprotection, bone health, renal and liver function and cognition have been uncovered. In the present article, we discuss the physiology of PGDP peptides and their therapeutic applications, with a focus on successful design of analogues including dual and triple PGDP receptor agonists currently in clinical development.

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Section: Discussionmentioning

confidence: 99%

Section: Glucagon-like Peptide-1mentioning

confidence: 99%

Proglucagon-Derived Peptides as Therapeutics

et al. 2021

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“…However, most of the data regarding the effect of gut hormones on the HPG axis in females have not been corroborated in human trials. The effects of gut hormones on the HPG axis in females also depend on fasting status and pubertal stage (78). Further investigations are needed to elucidate the exact stimulatory and inhibitory actions of these gut hormones and determine which species of the gut microbiome affects the gut hormone levels by producing SCFAs.…”

Section: Bile Acid-interleukin-22 Mechanismmentioning

confidence: 99%

The emerging role of the gut microbiome in polycystic ovary syndrome

Jin

Wang

et al. 2021

F&S Reviews

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Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder that affects women of reproductive age. Recent studies have demonstrated a close association between the gut microbiome and PCOS. Their microbial diversity may not significantly change, and the crucial role of Bacteroides spp. has been demonstrated in human PCOS. Furthermore, animal models of PCOS exhibit gut microbiome features different from those of humans with PCOS. The gut microbiome may differ in patients with PCOS because it can be affected by multiple PCOS-related factors. Dysbiosis of the gut microbiome may trigger PCOS symptoms via an underlying mechanism that may involve microbial metabolites, including bile acids, short-chain fatty acids, and lipopolysaccharides. The manipulation of the gut microbiome can affect PCOS phenotypes, and prebiotic or probiotic therapy has the potential to improve PCOS symptoms. Future mechanistic studies are required to identify the causative role of these microbes and their metabolites in the pathogenesis of PCOS.

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“…It was interesting to note that 24.66% of patients in the PCOS group started their rst menstruation after LSG within 7 days. However, the underlying mechanism of this phenomenon was unclear, which might be attributed to the changes in gastrointestinal hormones, insulin resistance, and hypothalamic-pituitary-adrenal axis right after LSG [ 37 ].…”

Section: The Menstrual Status Bmi and Use Of Oral Contraceptives Of Pcos Women With Obesity After Lsgmentioning

confidence: 99%

Predicting Menstrual Recovery After Laparoscopic Sleeve Gastrectomy in Polycystic Ovary Syndrome Women With Obesity

Cai

Zhang

Gao

et al. 2021

Preprint

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Objectives: To investigate the recovery of menses in polycystic ovary syndrome (PCOS) women with obesity after laparoscopic sleeve gastrectomy (LSG), and to explore the predictors for menstrual recovery. Methods: A total of 88 PCOS patients with obesity and 76 control patients with obesity aged 18-45 years were enrolled between May 2013 and December 2020. Preoperative clinical characteristics, metabolic parameters and sex hormones were collected. Postoperative menstrual status, body weight and use of oral contraceptives were obtained through telephone follow-up. Results: Patients with PCOS were followed up for at least six months after surgery, and the mean follow-up time was 3.23 years. About 24.66% of patients with PCOS started their first menstruation after LSG within 7 days, and 79.52% patients had regular menstruation at six months after LSG. In logistic regression analyses, duration of PCOS ≤4.5 years (P=0.007), number of preoperative menstruation per year >4.0 times/year (P=0.045), homeostatic model assessment of insulin resistance (HOMA-IR) ≤7.3 (P=0.020) and total testosterone (TT) ≤1.5 nmol/L (P=0.029) at baseline were significantly associated with menstrual resumption in PCOS patients within 6 months after LSG. After adjusting confounders, combination of four clinical indices at baseline could effectively predict menstrual recovery in PCOS patients within 6 months after LSG (AUC=0.837, [95%CI: 0.735-0.939], P<0.001). Conclusion: Overall, the combination of PCOS duration, menstruations per year, HOMA-IR and TT at baseline could be used as an effective tool for the prediction of menstrual recovery in PCOS patients within 6 months after LSG, which can be applied in preoperative evaluation.

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Emerging role of GIP and related gut hormones in fertility and PCOS

Cited by 32 publications

References 79 publications

Proglucagon-Derived Peptides as Therapeutics

Proglucagon-Derived Peptides as Therapeutics

The emerging role of the gut microbiome in polycystic ovary syndrome

Predicting Menstrual Recovery After Laparoscopic Sleeve Gastrectomy in Polycystic Ovary Syndrome Women With Obesity

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